Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain.
The relationship of neuronal DNA damage to tangle-bearing neurons and nitrotyrosine (NT) expression, a neurochemical marker of oxidative damage mediated by peroxynitrite, was examined in visual cortex of AD patients. Many terminal deoxynucleotidyl transferase (TdT)-positive neurons were detected and the majority (93%) of these TdT-labeled neurons lacked evidence of tangle formation. NT expression was elevated in AD cases and most TdT-labeled nuclei also showed strong NT immunoreactivity. These data suggest the hypothesis that the neurons with DNA damage in the absence of tangle formation may degenerate by tangle-independent mechanisms and that oxidative damage may contribute to such mechanisms in AD.
Su
J H
JH
Institute for Brain Aging and Dementia, University of California, Irvine, 92697-4540, USA. jsu@teri.bio.uci.edu
Deng
G
G
Cotman
C W
CW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D012016:Reference Values; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism* / Q000473:pathology
C002744:3-nitrotyrosine; D014443:Tyrosine; D004253:DNA Nucleotidylexotransferase